This proposal consists of four separate projects which are concerned with the problem of pores or channels in cell membranes. Project I is an investigation of the behavior of the channels formed by gramicidin in artificial lipid membranes based on measurements of the hydraulic and diffusive water permeability and the electro-osmotic coupling of the water and ion flux. These studies, using an approach that we have recently developed, provide unique information about the molecular dimensions of the channel, the partition of ions between the bulk solution and the channel and the transport kinetics in the channel. Project II is concerned with the measurements of the hydraulic water permeability and the diffusive permeability and reflection coefficient of the human erythrocyte membrane to small non-electrolytes. The measurements are based on the classical light scattering technique combined with several new experimental and theoretical modifications that we have developed. The effects of a number of different inhibitors on the reflection coefficient and the water and solute permeability will be measured. The investigation is directed towards the question of whether the water is moving through channels associated with the solute transport system. Project III is a computer simulation (molecular-dynamics) study of the behavior of an ion channel similar to gramicidin. The computer provides an exact solution to a specific model of the channel and the motion of the ion and channel atoms can be followed directly. Project IV is an attempt to trap glucose in the binding site of the glucose transport system of the human red cell. The experiments are based on the idea that the glucose transport system is in a pore with a binding site that undergoes a conformational change. Non-specific protein reagents that react at the ends of the pore should be able to irreversibly block the glucose in the transport system. If successful, this approach should provide a general procedure for labeling, isolating and studying solute transport systems.